Subacute Stage Research Articles

Deciphering temporal gene expression dynamics during epilepsy development using a rat model of focal neocortical epilepsy

AbstractObjectiveEpilepsy involves significant changes in neural cells during epileptogenesis. Although the molecular mechanism of epileptogenesis remains obscure, changes in gene regulation play a crucial role in the evolution of epilepsy. This study aimed to compare changes in a subset of specific genes during epilepsy development, focusing on the period after the first spontaneous seizure, to identify critical time windows for targeting different regulators.MethodsUsing a rat model of acquired focal neocortical epilepsy induced by tetanus toxin, we characterized gene expression at acute, subacute, and chronic stages (48–72 h, 2 weeks, and 30 days after first spontaneous seizure, respectively), focusing on genes' potential contribution to epilepsy progression.ResultsWe observed dynamic changes in the expression of these genes throughout the period after the first spontaneous seizure. Astrocytic reactions primarily occur early, before epilepsy is well established. Changes in Mtor (mammalian target of rapamycin) and Rest (repressor element 1 silencing transcription factor) signaling pathways are highly dynamic and correlated with the progression of epilepsy development. Ccl2 (chemokine C‐C‐motif ligand) is upregulated at the chronic stage, indicating activation of the neuroinflammatory pathway. Finally, Gabra5 (γ‐aminobutyric acidergic signaling) is downregulated at the late stage after epilepsy is established. Surprisingly, changes in the expression of specific genes are linked to the time since the first seizure, rather than seizure frequency or duration.SignificanceThese results suggest that the regulation of specific genes is essentially stage‐dependent during the development of epilepsy, highlighting the importance of targeting specific genes at appropriate stages of epilepsy development.

Dissociation of White Matter Bundles in Different Recovery Measures in Poststroke Aphasia.

Poststroke aphasia (PSA) recovery shows high variability across individuals and at different time points. Although diffusion biomarkers from the ventral and dorsal streams have demonstrated strong predictive power for language outcomes, it is still unclear how these biomarkers relate to the various stages of PSA recovery. In this study, we aim to compare diffusion metrics and language measures as predictors of language recovery in a longitudinal cohort of participants with PSA. Participants were recruited at a stroke unit at the emergency room, and underwent diffusion magnetic resonance imaging scanning and language assessment within 3 days (acute phase) after stroke, with behavioral follow-ups at subacute (10±3 days) and chronic phases (>6 months). We conducted regression analyses on language performance (cross-sectional), Δscores between all time points (acute-subacute, subacute-chronic, acute-chronic), and relative Δscores between all time points (Δscore/language baseline score), with acute diffusion metrics from language-related white matter tracts, lesion size, language baseline scores, and demographic data as predictors. Thirty-nine participants presenting PSA were recruited, and 24 participants (mean age, 73 years; 8 women) completed the 3-time point assessment in total. The best prediction model of performance scores used axial diffusivity from the left arcuate fasciculus in both the subacute (R2=0.785) and chronic stages (R2=0.626). Moreover, the prediction of ∆scores depended on axial diffusivity from the left inferior frontal-occipital fasciculus in the subacute stage (R2=0.5) and depended additionally on axial diffusivity from the right inferior frontal-occipital fasciculus in the chronic stage (R2=0.68). The prediction of mediation analyses showed that the lesion load of the left arcuate fasciculus mediated the relationship between axial diffusivity from the left arcuate fasciculus and chronic language performance. Language performance at subacute and chronic time points could be predicted by the integrity of the left arcuate fasciculus, whereas Δscores in the subacute and chronic phases depended on the left inferior frontal-occipital fasciculus, showing a dissociation of the white matter pathways about language outcomes. These results suggest a functional differentiation of the dual-stream components in PSA recovery.

Remote ischemic preconditioning plays a neuroprotective role in cerebral ischemia-reperfusion mice by inhibiting mitophagy

Remote ischemic preconditioning (RIPC) represents a clinically feasible method for safeguarding vital organs against ischemic injury. However, its specific role in cerebral ischemia-reperfusion (I/R) injury remains to be definitively elucidated. In this study, we investigated the neuroprotective effects of RIPC on mice at 7 days post-cerebral I/R and its involvement in mitophagy and mitochondrial dysfunction. Cerebral I/R led to impaired brain function, as well as structural and functional damage to mitochondria. Notably, RIPC treatment ameliorated the neurological dysfunction induced by cerebral I/R. Compared with the I/R group, the expression levels of NeuN, MBP, PDH, and Tom20 were significantly elevated in the RIPC + I/R group. Furthermore, mitochondria in the RIPC + I/R group exhibited more intact structure compared to those in the I/R group. In mice subjected to I/R injury, RIPC treatment markedly increased ATP content, ADP content, TAN level and glucose uptake while upregulating expression levels of Parkin, Pink1 and P62 proteins; it also reduced both the volume of ischemic foci and the number of mitochondrial autophagosomes along with decreasing LC3B II/I ratio. In conclusion, RIPC may exert a neuroprotective role by inhibiting excessive mitophagy during subacute stages following an ischemic stroke.

Cold atmospheric plasma-activated saline alleviates secondary injury post-SCI by inhibiting extracellular matrix remodeling and infiltration of proinflammatory macrophages

BackgroundCold atmospheric plasma (CAP) has been shown to improve the recovery of transected peripheral nerves. We determined the protective role of CAP-activated saline (CAP-AS) treatment in the acute and subacute stages of spinal cord injury (SCI) in mice. MethodsC57BL/6 SCI mice were treated with CAP-AS for 14 days. Injury recovery was assessed weekly for four weeks by conducting motor function tests, including the Basso Mouse Scale (BMS) and footprint test. Transcriptome analysis was conducted on day 14 to elucidate potential mechanisms, which were further validated through immunofluorescence examinations of the injured spinal cord tissues on day 28 and the levels of proinflammatory cytokines produced by macrophages in vitro. ResultsCompared to the SCI group, the CAP-AS-treated groups presented significantly better hindlimb motor function after four weeks. The downregulated (SCI vs. SCI + CAP-AS, with CAP-AS activated for 20 min) differentially expressed genes (DEGs) were enriched in the extracellular region, extracellular matrix (ECM), and ECM-receptor interaction. In contrast, the upregulated DEGs were enriched in immune response-associated pathways. Histological changes in the CAP-AS-treated groups were observed to further validate the predicted mechanisms 28 days post-injury. The alleviation of secondary injury was confirmed by an increase in GFAP-positive and NFH-positive areas, and enhanced outgrowth of 5-HT-positive fibers. Inhibited ECM remodeling was confirmed by a decrease in the areas positive for PDGFRβ, fibronectin, and laminin. A decrease in the infiltration of macrophages and activation of microglia was determined by a decrease in CD68-positive and F4/80-positive areas. The inhibitory effect of CAP-AS on inflammation was further supported by a decrease in the levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α in CAP-AS-treated M1 macrophages. ConclusionCAP-AS can alleviate secondary injury in SCI model mice by inhibiting ECM remodeling in injured tissues and reducing the infiltration or activation of proinflammatory macrophages/microglia.

Longitudinal evaluation of circumpapillary structure-function and vasculature-function relationships in acute and sub-acute nonarteritic anterior ischemic optic neuropathy

PurposeTo investigate the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) using circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements, circumpapillary vessel density (cpVD) and the corresponding/final visual outcomes at different stages of nonarteritic anterior ischemic optic neuropathy (NAION). MethodsThirty eyes of 30 patients with acute NAION were included. LogMAR best-corrected visual acuity(BCVA), mean deviation (MD) and visual field index (VFI), cpRNFL thickness and cpVD across different retinal layers were examined at baseline, 2 weeks and 1 month after diagnosis. Potential correlations between the Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters and visual outcomes were investigated in both acute and sub-acute NAION. ResultsSignificant global and regional correlations in S-F relationship were identified exclusively in sub-acute stage (p < 0.05). However, among the OCTA parameters for the acute NAION, the temporal cpVD in superficial vessel complex (SVC) and inner retinal layer (IRL) exhibited positive correlations with corresponding and final visual acuity and visual field outcomes. In the sub-acute stage of NAION, the cpVD of global or temporal section in radial peripapillary capillary (RPC), SVC and IRL were positively correlated with visual outcomes. ConclusionSignificant longitudinal V-F relationships exist both globally and regionally, in acute and sub-acute NAION. The cpVD parameters of the SVC and IRL are potentially valuable for evaluating corresponding and final visual outcomes and highlights the importance of monitoring cpVD over cpRNFL thickness in acute NAION.

Fast diffusion kurtosis imaging for venous stroke caused by cerebral venous thrombosis

Background: Diffusion kurtosis imaging (DKI) has been found to be more precise than diffusion weighted imaging (DWI) for detecting irreversible infarction in acute ischemic stroke. This study aimed to evaluate whether fast DKI has distinctive advantages in detecting venous stroke caused by cerebral venous thrombosis (CVT). Methods: All data from patients diagnosed with venous stroke due to CVT and qualified for mechanical recanalization treatment were collected. Fast DKI and DWI were obtained both before and after revascularization therapy, and lesions were measured. Lesion volumes on T2 weighted imaging (T2WI) were followed up at six months. Results: A total of 11 patients were recruited. Compared to the contralateral brain, ADC values of the lesions in pre-operation increased significantly (1340.12±235.42 vs 919.75±128.98, P &lt; 0.05), while MK decreased (0.59±0.11 vs 0.81±0.12, P &lt; 0.05). And the same changing trend about ADC values (1258.94±185.08 vs 949.81±148.52, P &lt; 0.05) and MK values (0.64±0.12 vs 0.83±0.12, P &lt; 0.05) in post-operation. There was no significant difference in the volume of lesions between DKI and DWI during the same examination period (26.97 vs 29.28, Ppre &gt; 0.05; 13.34 vs 13.14, Ppost &gt; 0.05). However, the lesion volume after revascularization was significantly reduced compared to the first DKI and DWI examinations (26.97 vs 13.34, P &lt; 0.05), and the same as DWI (29.28 vs 13.14, P &lt; 0.05). Volume of T2WI lesions after the 6th month diminished significantly compared with both DKI lesions and DWI lesions before treatment (7.25 vs 26.97, P &lt; 0.05; 7.25 vs 31.19, P &lt; 0.05). Fast DKI had a higher signal to noise ratio (SNR) than traditional DKI and DWI. Conclusion: The MK of the venous stroke lesions decreased significantly in the subacute stage of CVT, suggesting reversible infarction. Fast DKI has more distinctive superiority in the evaluation of venous stroke. Fast DKI approach may hold great promise for patients in clinical setting because of a higher SNR than DWI. But the sample need to be further expanded because of only 11 patients recruited.

Anxiety and Depression after Spinal Cord Injury: A Cross-Sectional Study.

Spinal cord injury (SCI) is a life-changing event that often results in chronic physical damage and challenges in maintaining a good quality of life as it affects every aspect of life. These situations require adjustment, increasing vulnerability to psychological disorders. The objective of this study was to evaluate the impact of SCI on psychological morbidity in individuals with subacute and chronic SCI. The present investigation was designed to determine the presence and extent of psychological complications following SCI. We used two reliable questionnaires and validated psychological assessments to study depression (BDI) and anxiety (STAI), a broad range of factors derived from SCI that may be predictors of certain psychological problems. The psychological assessment revealed alterations in depression and anxiety, although the data do not exceed those of previous investigations. No clear predisposing factors leading to certain psychological pathologies were found. In addition, individuals in the subacute and chronic stages differed in their scores. In individuals with SCI, identifying predictors of psychological problems is difficult, but premature assessment of mental state is essential. This early diagnosis of possible problems or changes at the mental level is fundamental and necessary to avoid possible alterations at the cognitive level and, of course, more serious mental complications.

Brain white matter pathways of resilience to chronic back pain: a multisite validation.

Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have pointed to brain characteristics as predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking. In two independent longitudinal studies, we examined white matter diffusion imaging data and pain characteristics in patients with subacute back pain (SBP) over six- and 12-month periods. Diffusion data from individuals with CBP and healthy controls (HC) were analyzed for comparison. Whole-brain tract-based spatial statistics analyses revealed that a cluster in the right superior longitudinal fasciculus (SLF) tract had larger fractional anisotropy (FA) values in patients who recovered (SBPr) compared to those with persistent pain (SBPp), and predicted changes in pain severity. The SLF FA values accurately classified patients at baseline and follow-up in a third publicly available dataset (Area under the Receiver Operating Curve ∼ 0.70). Notably, patients who recovered had FA values larger than those of HC suggesting a potential role of SLF integrity in resilience to CBP. Structural connectivity-based models also classified SBPp and SBPr patients from the three data sets (validation accuracy 67%). Our results validate the right SLF as a robust predictor of CBP development, with potential for clinical translation. Cognitive and behavioral processes dependent on the right SLF, such as proprioception and visuospatial attention, should be analyzed in subacute stages as they could prove important for back pain chronicity.

The association between dexterity and upper limb impairment during stroke recovery.

Stroke-induced upper limb disabilities can be characterized by both motor impairments and activity limitations, commonly assessed using Fugl-Meyer Motor Assessment for Upper Extremity (FMMA-UE) and Action Research Arm Test (ARAT), respectively. The relationship between the two assessments during recovery is largely unstudied. Expectedly they diverge over time when recovery of impairment (restitution) plateaus, but compensation-driven improvements still occur. The objective of this study is to evaluate the alignment between FMMA-UE and ARAT in defining upper limb functional recovery categories by ARAT scores. We aimed to establish cut-off scores for both measures from the acute/early subacute, subacute and chronic stages of stroke recovery. Secondary analysis of four prospective cohort studies (acute/early subacute: n = 133, subacute: n = 113, chronic: n = 92) stages post-stroke. Receiver operating characteristic curves calculated the area under the curve (AUC) to establish optimal FMMA-UE cut-offs based on predefined ARAT thresholds distinguishing five activity levels from no activity to full activity. Weighted kappa was used to determine agreement between the two assessments. We used minimally clinically important difference (MCID) and minimal detectable change (MDC95) for comparison. FMMA-UE and ARAT scores showed no relevant divergence across all recovery stages. Results indicated similar cut-off scores in all recovery stages with variability below MCID and MDC95 levels. Cut-off scores demonstrated robust AUC values from 0.77 to 0.86 at every recovery stage. Only in highly functional patients at the chronic stage, we found a reduced specificity of 0.55. At all other times sensitivity ranged between 0.68 and 0.99 and specificity between 0.71 and 0.99. Weighted kappa at the acute/early subacute, subacute and chronic stages was 0.76, 0.83, and 0.81, respectively. Our research shows a strong alignment between FMMA-UE and ARAT cut-off scores throughout stroke recovery, except among the subgroup of highly recovered patients at the chronic stage. Discrepancies in specificity potentially stem from fine motor deficits affecting dexterity outcomes that are not captured by FMMA-UE. Additionally, the high congruence of both measures suggests they are not suited to distinguish between restitution and compensation. Calling for more comprehensive assessment methods to better understand upper limb functionality in rehabilitation.

Recovery of Learning and Memory Deficits Despite Persistent Pyknosis of the Hippocampal Pyramidal Neurons of Adult Hydrocephalic Mice.

The hippocampal alterations resulting from hydrocephalus are associated with various cognitive dysfunctions. Reduced learning and memory are early functional deficits that recover with time in experimental hydrocephalus. This study investigated the recovery processes of learning and memory loss in relation to the morphology of hippocampal pyramidal neurons and the degree of expansion of the ventricles. Hydrocephalus was induced in adult mice by intracisternal injection of sterile kaolin while controls received sham operation. Neurobehavioral tests for memory and learning were conducted, after which the animals were sacrificed in batches: 7 (acute) and 28 (subacute) days postinduction. After sacrifice, mice were categorized into mild and moderate hydrocephalus, and their fixed brain samples were processed for hematoxylin, eosin, and Nissl stains. In moderate acute hydrocephalus, the indices of learning and memory were reduced escape latency (67.20 ± 12.83 s), number of platform crossing (4.000 ± 1.658), duration in platform quadrant (4.000 ± 1.658), and percent of total investigation (44.857% ± 3.981%) but not in the subacute stage. Pyknotic indices (PI) were significantly higher in the cornu ammonis (CA)1 and 3 regions in all hydrocephalic groups than in controls. However, within groups, PI was significantly higher only in the CA1 of moderate acute (28.149% ± 1.875%) compared to moderate subacute hydrocephalic group (12.903% ± 3.23%). Hydrocephalus caused cellular injury to the hippocampus associated with spatial learning and memory deficits. However, these functional deficits were partially reversed in moderate subacute hydrocephalus despite the persistence of the structural alterations in the CA1 and CA3 subregions.

Untargeted blood serum proteomics identifies novel proteins related to neurological recovery after human spinal cord injury

BackgroundThe discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results.MethodsIn this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA).ResultsOur findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery.ConclusionsOur study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.

Beyond the chronic pain stage: default mode network perturbation depends on years lived with back pain.

Research has indicated that the default mode network (DMN) is perturbated in patients with chronic pain when compared with healthy controls, and this perturbation is correlated with the duration of pain during the chronic pain stage. It remains unclear whether DMN adaptations manifest during the subacute pain stage and progress over time because of the duration of pain experience, rather than being a specific correlate of the chronic pain stage. Furthermore, information regarding whether these adaptations are related to cognitive processes of adaptation is lacking. To this end, we examined the DMN in 31 patients with chronic back pain (CBP), 77 patients with subacute back pain (SBP), as well as 39 healthy pain-free controls (HC) applying a graph-theoretic network approach on functional resting-state magnetic resonance imaging. Beyond the comparison between groups, we used a linear analysis considering the years lived with pain (YLP) across all patients with back pain and additionally performed a mediation analysis of the role of cognitive pain coping. In line with previous studies, we found significant DMN perturbation in CBP compared with HC. However, this did not apply to the comparison of CBP with SBP. Instead, we observed a positive correlation between DMN perturbation and YLP. This was significantly mediated by coping attitudes towards pain. Default mode network perturbation may thus reflect neural adaptation processes to pain experience rather than a single correlate of the chronic pain stage and be modulated by cognitive adaption. This points to potentially underinvestigated significant adaptation processes that could enable more fine-grained patient stratification.

SEPTIC COMPLICATIONS AFTER THE USE OF GLUCOCORTICOIDS (RESULTS OF CLINICAL LABORATORY AND PATHOMORPHOLOGICAL STUDIES)

In numerous articles, monographs, and textbooks, the aspects of local application of glucocorticoid injections at the current stage of development of rheumatology are considered from the point of view of expediency, effectiveness, and safety. Factors affecting the effectiveness of this method are analyzed. Periarticular and/or intra-articular injections of corticosteroids are included in various recommendations and protocols for the treatment of arthrosis and rheumatic joint lesions available today. Objective. Determination of pathomorphological, clinical and laboratory manifestations of the infectious process after local administration of glucocorticoid drugs. Methods. Clinical, anamnestic, laboratory, bacteriological and pathomorphologicaldata of 34 patients with infectious complications were analyzed. Results. The administration of long-acting drugs was most often used: DIPROSPAN — 13 (38.2 %) cases; KENALOG — 5 (14.7 %); DEPOS — 3 (8.8 %); FLOSTERON — 2 (5.9 %); a short-acting drug (methylprednisolone acetate (METYPRED), hydrocortisone acetate) was used in 11 (32.4 %) cases. At the time of hospitalization in the clinic, the infectious process was in 8 (23.5 %) patients in the acute stage, 10 (29.4 %) in the subacute stage, and in another 16 (47.1 %) in the chronic stage, 13 (38.2 %) of which are in the active fistula phase. Conclusions. Pathomorphological manifestations and signs of a purulent-necrotic and purulent-inflammatory infectious process (infectious complications) after local administration of glucocorticoid drugs accompany and are closely statistically significantly interrelated with typical clinical and laboratory manifestations (leukocytosis with a «shift of the leukocyte formula to the left», an increase in ESR and level CRP) and etiology («bacteriology») of the infectious process.

The incidence of periungual desquamation and thrombocytosis in Kawasaki disease and the importance of systematic observation in the subacute phase.

Periungual desquamation and thrombocytosis are characteristic of the subacute phase of Kawasaki disease (KD). However, accurate observations of periungual desquamation and thrombocytosis are lacking. This retrospective study included patients with acute-phase KD who received treatment at seven affiliated university hospitals in Korea between 2015 and 2017. Data were extracted from an anonymized registry established by the Korean Society of Kawasaki Disease. We investigated whether the findings of patients observed according to a set protocol until the subacute stage (group I) were different from those of patients observed without the use of a protocol (group II). A total of 879 patients with KD were included in the analysis. Periungual desquamation was observed in 85% and 12.7% of patients in groups I and II, respectively. Thrombocytosis was observed in 76.7% and 44.7% of patients in groups I and II, respectively. Furthermore, compared to the initial test, the platelet counts of patients increased 100% and 67.9% in group I and II, respectively. When incomplete KD was defined only by the main symptoms during the acute stage and the diagnostic criterion of periungual desquamation during the subacute stage was excluded, the significant difference in the incidence of incomplete KD between groups I and II was no longer apparent. Performing regular and detailed observations has resulted in a higher incidence of periungual desquamation and thrombocytosis during the subacute phase of KD than those reported in recent studies. This indicates that until now, we have been neglecting the observation of symptoms and signs during the subacute phase. Regular monitoring during this period can also aid in differentiating suspected cases of KD and facilitate appropriate follow-up of complications.

Comparison of Bilateral Versus Unilateral 5 Hz or 1 Hz Repetitive Transcranial Magnetic Stimulation in Subacute Stroke: Assessment of Motor Function in a Randomized Controlled Study.

Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity after stroke. At low frequencies, rTMS has an inhibitory effect, whereas at high frequencies, it has an excitatory effect. Combining both frequencies in bilateral stimulation is a new rTMS protocol under investigation, especially in the subacute stage. Fifty-five patients with subacute stroke were divided into four groups according to the rTMS protocol delivered: bilateral, inhibitory, excitatory, and control groups. All groups received concomitant task-oriented physiotherapy. Pretreatment to posttreatment assessment was performed twice, immediately after sessions and 1 month later. Volitional motor control was evaluated by Fugl-Meyer and Wolf motor function tests, and for spasticity, the Ashworth scale was used. All groups showed significant improvement. Bilateral, inhibitory, and excitatory groups showed same efficacy, but the bilateral protocol was superior in spasticity. No correlations were found between improvement and stroke duration and site except for spasticity. Bilateral rTMS shows a comparable effect to inhibitory and excitatory rTMS in improving motor disability in subacute stroke. However, it is superior for spasticity.

Polish Cultural Adaptation and Reliability of the Fugl-Meyer Assessment of Motor Performance and Sensory Assessment Scale in Stroke Patients.

Background and Purpose: The Fugl-Meyer Assessment of Motor Performance and Sensory Assessment Scale (FMA) is the most commonly used and recommended outcome measure for the sensorimotor impairment of the upper and lower limbs in stroke patients. The aim of this study was to perform cross-cultural translation and adaptation of the scale into Polish and to evaluate the FMA's reliability of motor performance and sensation of the upper and lower limb sections among ischemic stroke patients. Methods: The Polish version of the FMA (FMA-PL) was developed using a forward-backward translation performed by a group of experts and then evaluated by a panel of judges according to international guidelines. The study involved 86 patients (F = 30, M = 56, i.e., 35%; the average age of patients was 64 ± 12 years, 36 with right-sided stroke and 50 with left-sided stroke). The FMA-PL was carried out twice by two experienced neurological physiotherapists with a 2 h gap between assessments (test-retest and inter-rater). The reliability of the outcome measure was defined by calculating the intraclass correlation coefficient (ICC). The standard error of measurement (SEM) and the minimum detectable change (MDC) were also calculated. The internal consistency of the test was determined by the Cronbach's alpha indicator. Results: Three domains were evaluated on the FMA-PL scale. From the whole test, results were obtained in the range of 12-124 points: 64 points for FMA-UE-PL 2, 34 points for FMA-LE-PL 4, and 24 points for FMA-S-PL 0. The ICC values were in the range of 0.99-1.00 for the total FMA-PL score and the results of each domain. The SEM and MDC for the entire FMA-PL calculated for test-retest measurements were 0.22 and 1.60, respectively. The SEM and MDC for the total FMA-PL score obtained during repeated measurements of the same investigator were 1.3 and 3.5 points, respectively. The Cronbach's alpha values calculated for the total FMA-PL, FMA-UE-PL, FMA-LE-PL, and FMA-S-PL items amounted to 0.938-0.939, 0.932-0.934, and 0.634-0.722, respectively. Conclusions: The Polish version of the FMA is a consistent and reliable outcome measure for the motor and sensory evaluation of the upper and lower limbs for patients in subacute and chronic stroke stages.

High-intensity interval training is feasible, credible and clinically effective in the early subacute stroke stage in the low-income country of Benin

ABSTRACT High-intensity interval training (HIIT) has been shown to benefit stroke patients when implemented three months post-stroke. This study examined HIIT’s feasibility and clinical effectiveness in the early post-stroke stage in Benin. This was a prospective interventional study comprising an HIIT programme executed on a recumbent bike, three times/week, 20–30 min/session for 6 weeks, added to a conventional physiotherapy. The primary outcomes were feasibility, credibility and expectancy assessed with credibility and expectancy questionnaire. A maximal exercise test, 6-min walking test (6MWT), 10-m walking test (10mWT), Berg balance scale (BBS) and five repetitions sit-to-stand test (5 R-STS) were performed before and after the training programme. Ten outpatients, with a median age [P25-P75]: 63.5[56.7–71.2] years; time since stroke: 15.0[9.7–21.0] days, started and completed all training sessions without serious adverse events. High scores were observed on the Credibility subscale at admission (27.0[25.7–27.0]), which remained so after intervention (26.5[25.7–27.0]). Expectancy subscale scores were high at admission (25.5[24.0–27.0]) and post-training (25.5[24.5–27.0]). Peak workload (p < 0.001), BBS (p < 0.001), 6MWT (p < 0.001), 10mWT (p < 0.001) and 5 R-STS (p = 0.004) were all improved. HIIT is feasible and safe in the early subacute post-stroke stage and is perceived by patients as highly credible, meeting their expectations of recovery.

Corticomotor pathway function and recovery after stroke: a look back and a way forward.

Stroke is a leading cause of adult disability that results in motor deficits and reduced independence. Regaining independence relies on motor recovery, particularly regaining function of the hand and arm. This review presents evidence from human studies that have used transcranial magnetic stimulation (TMS) to identify neurophysiological mechanisms underlying upper limb motor recovery early after stroke. TMS studies undertaken at the subacute stage after stroke have identified several neurophysiological factors that can drive motor impairment, including membrane excitability, the recruitment of corticomotor neurons, and glutamatergic and GABAergic neurotransmission. However, the inherent variability and subsequent poor reliability of measures derived from motor evoked potentials (MEPs) limit the use of TMS for prognosis at the individual patient level. Currently, prediction tools that provide the most accurate information about upper limb motor outcomes for individual patients early after stroke combine clinical measures with a simple neurophysiological biomarker based on MEP presence or absence, i.e. MEP status. Here, we propose a new compositional framework to examine MEPs across several upper limb muscles within a threshold matrix. The matrix can provide a more comprehensive view of corticomotor function and recovery after stroke by quantifying the evolution of subthreshold and suprathreshold MEPs through compositional analyses. Our contention is that subthreshold responses might be the most sensitive to reduced output of corticomotor neurons, desynchronized firing of the remaining neurons, and myelination processes that occur early after stroke. Quantifying subthreshold responses might provide new insights into post-stroke neurophysiology and improve the accuracy of prediction of upper limb motor outcomes.

Augmented Central Pain Processing Occurs after Osteoporotic Vertebral Compression Fractures and Is Associated with Residual Back Pain after Percutaneous Vertebroplasty.

A retrospective analysis. To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP). RBP is a vexing complication that affects 6.3%-17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients' psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication. Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05). Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.

Leber Hereditary Optic Neuropathy (LHON): Genetics and Ophthalmology Case Repo

It is important to recognize that this clinical case demonstrates that carriers can remain asymptomatic, there may be changes recognizable in the ophthalmological examination. The clinical onset of Leber hereditary optic neuropathy (LHON) usually occurs in young adulthood (ages 18-30) and is divided into subacute (&lt;6 months from onset) and dynamic (6-12 months) stages. It is caused by a mitochondrial mutation that is transmitted from mothers to children. It is the most common inherited mitochondrial disorder, but it is considered a rare disease. It usually causes severe vision loss in both eyes. The classic presentation of LHON is that of a young adult male who develops a severe, painless, acute or subacute unilateral vision loss, followed by a similar vision loss in the fellow eye two to three months later (although rarely the delay can be much longer). In most cases, it starts affecting only one eye and, within a few weeks or months, affects the second eye. It can all be seen with the loss of the pupil's ability to react to light. Complete blindness is rare among patients suffering from this disease.